Efficacy and Tolerability of Exenatide Once Weekly Over 6 Years in Patients with Type 2 Diabetes: An Uncontrolled Open-Label Extension of the DURATION-1 Study

Diabetes Technol Ther. 2016 Nov;18(11):677-686. doi: 10.1089/dia.2016.0107. Epub 2016 Aug 15.

Abstract

Background: Long-term treatment is necessary to slow the progression of type 2 diabetes (T2D). Here, we examined the safety and efficacy of 6 years of treatment with exenatide once weekly (QW) among patients with T2D in the DURATION-1 trial.

Methods: The study enrolled patients aged ≥16 years with T2D treated primarily with metformin and sulfonylureas. Following 30 weeks of randomized treatment with exenatide QW 2 mg or exenatide twice daily 10 μg, patients entered an uncontrolled, open-label, open-ended study phase in which all patients received exenatide QW 2 mg. Restrictions on concomitant medication use were eased over time.

Results: Of the original 295 patients in the intent-to-treat population, 136 (46%) completed 6 years of treatment. Six-year completers had sustained significant improvements from baseline in glycated hemoglobin (HbA1c; least-squares mean [LSM] change, -1.6%), with 46.3% achieving HbA1c <7.0%, 33.1% achieving HbA1c ≤6.5%, and significant improvements from baseline in fasting plasma glucose (-28 mg/dL) and body weight (-4.2 kg) at 6 years. The 78 completers who added no glucose-lowering medications had numerically greater body weight reductions than the overall cohort (6-year LSM change, -6.1 kg) with more stability over time. No unexpected adverse events were observed during 1202.4 patient-years of exposure. Most minor hypoglycemia events occurred with concomitant sulfonylurea use.

Conclusions: Exenatide QW was associated with clinically significant, sustained improvements in glycemic control and weight in patients who continued therapy for up to 6 years, without unexpected safety findings. ClinicalTrials.gov registration: NCT00308139.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Blood Glucose
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Exenatide
  • Female
  • Glycated Hemoglobin A
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Peptides / administration & dosage
  • Peptides / adverse effects
  • Peptides / therapeutic use*
  • Treatment Outcome
  • Venoms / administration & dosage
  • Venoms / adverse effects
  • Venoms / therapeutic use*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • Exenatide

Associated data

  • ClinicalTrials.gov/NCT00308139